title: Attenuation of pain-related behavior evoked by injury through blockade of neuropeptide Y Y2 receptor.
abstract: Neuropeptide Y (NPY) has an important but still insufficiently defined role in pain modulation. We therefore examined the ability of NPY to modulate experimentally induced neuropathic pain by injecting it directly into dorsal root ganglion (DRG) immediately following spinal nerve ligation (SNL) injury. We have found that this application exacerbates pain-related behavior induced by SNL in a modality-specific fashion. When saline was injected after SNL, the expected increase in hyperalgesia responses to needle stimulation was present on the 8th postoperative day. When we injected NPY, hyperalgesic responses were increased in a manner similar to the SNL/saline group. To characterize NPY action, specific Y1 and Y2 antagonists were also delivered directly to DRG, which revealed that behavioral actions of NPY were abolished by Y2 receptor antagonist. We tested whether NPY effects were the result of its role in immunity by immunohistochemical staining for glial fibrillary acidic protein, in order to identify activation of DRG satellite cells and dorsal horn astrocytes. Exacerbation of pain-related behavior following NPY injection was accompanied by astrocyte activation in ipsilateral dorsal horn and with satellite cells activation in the DRG proximal to injury. This activation was reduced following Y2 receptor antagonist application. These findings indicate an important link between pain-related behavior and neuroimmune activation by NPY through its Y2 receptor.
authors.affiliation: Laboratory for Pain Research, Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, Split 21000, Croatia.
authors.forename: Damir
authors.initials: D
authors.lastname: Sapunar
authors.forename: Katarina
authors.initials: K
authors.lastname: Vukojević
authors.forename: Sandra
authors.initials: S
authors.lastname: Kostić
authors.forename: Livia
authors.initials: L
authors.lastname: Puljak
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D045442:Rotarod Performance Test / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D001552:Benzazepines; D005904:Glial Fibrillary Acidic Protein; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D001120:Arginine; C403256:BIIE 0246; C117416:BIBO 3304